Revolutionizing the Fight Against Visceral Leishmaniasis: A New Diagnostic Breakthrough

The WHO's new Target Product Profile (TPP) outlines essential features for a diagnostic test to confirm the cure of visceral leishmaniasis (VL). This initiative aims to develop a reliable, non-invasive test to improve VL management, especially in endemic regions.

In a significant step towards combating visceral leishmaniasis (VL), the World Health Organization (WHO) has developed a Target Product Profile (TPP) for a diagnostic test to confirm the cure of this deadly disease. This initiative, spearheaded by the Global Neglected Tropical Diseases Programme, aims to outline the essential features and ideal characteristics of a new diagnostic test to ensure the effective post-treatment confirmation of VL cure.

Understanding Visceral Leishmaniasis

Visceral leishmaniasis, also known as kala-azar, is a severe disease caused by protozoan parasites transmitted through the bites of infected female phlebotomine sandflies. This disease predominantly affects impoverished regions, with most cases reported in Brazil, Eastern Africa, and India. Characterized by fever, weight loss, enlargement of the spleen and liver, and anemia, VL can be fatal if not treated promptly. Annually, an estimated 50,000 to 90,000 new cases are reported worldwide, highlighting the urgent need for effective diagnostic tools.

Current Diagnostic Challenges

Early detection and treatment are critical in controlling VL. Presently, the diagnosis involves serological tests such as the direct agglutination test and the rK39 antigen-based immunochromatographic tests. However, these tests are limited by their inability to confirm a cure due to the persistence of antibodies even after treatment. This gap in the diagnostic process underscores the necessity for a new, non-invasive in vitro test that can reliably confirm the cure of VL.

The Development of the Target Product Profile

Recognizing the need for improved diagnostic tools, WHO established the Diagnostic Technical Advisory Group (DTAG) to address the diagnostic needs for neglected tropical diseases (NTDs). A dedicated subgroup focused on VL was formed to develop the TPP, identifying key priorities and characteristics required for the new diagnostic test. This effort is part of WHO's broader strategy to enhance diagnostic capacities and combat NTDs more effectively.

The TPP for the diagnostic test to confirm VL cure outlines both minimum and ideal characteristics across various aspects. The intended use of the test is to detect analytes specific to Leishmania donovani and/or L. infantum to confirm cure. It should apply to individuals of all ages and genders who have been treated for VL. The infrastructure requirements specify that laboratory-based tests can be performed in health facilities, while point-of-care tests should operate under zero-infrastructure conditions. Training requirements indicate that trained technicians should perform laboratory tests, whereas point-of-care tests should be administered by health personnel or community workers with minimal training.

In terms of design, laboratory-based tests should require standard equipment, while point-of-care tests should be highly portable. Laboratory tests can utilize mains power and laboratory-grade water, whereas point-of-care tests should be self-contained. The tests should accommodate blood (finger stick or venous), urine, or saliva with minimal preparation. Performance specifications include a minimum diagnostic sensitivity of 85% and a specificity of 99% for laboratory tests. Laboratory tests should deliver results within 24 hours, while point-of-care tests should provide results within 0.5 hours. Results with high throughput capacities should remain stable for at least 0.5 hours.

Moving Forward

The development of a reliable, non-invasive diagnostic test to confirm VL cure has the potential to transform the management and control of this disease. The TPP by WHO provides a comprehensive framework to guide this development, ensuring that the new diagnostic tool meets the necessary standards and can be effectively utilized in endemic regions.

This initiative aims to enhance treatment outcomes and support global efforts to eliminate visceral leishmaniasis as a public health problem by addressing the current limitations of VL diagnostics.